Top cancer research advances at MSK in 2024

Peer-Reviewed Publication

Memorial Sloan Kettering Cancer Center

image:

An immunofluorescence image of an aged mouse liver. Expression of β-galactosidase (white) and uPAR (yellow) in senescent cells serve as target for engineered CAR T cells. Elimination of these cells improved age-related metabolic dysfunction.

The ability to improve age-related metabolic dysfunction by targeting senescent cells with engineered CAR T cells was just one of many discoveries made by MSK researchers in 2024.view more

Credit: Memorial Sloan Kettering Cancer Center

Researchers at Memorial Sloan Kettering Cancer Center (MSK) continued to make strides against cancer in 2024. Laboratory research teams across the institution worked to advance the global understanding of cancer and to develop new therapies, while also making fundamental insights into human biology and disease.

“Patients come to MSK seeking the very best in cancer care, which is driven by our commitment to cancer research,” said MSK President and CEO Selwyn M. Vickers, MD, FACS. “MSK scientists continue to expand our understanding of cancer and to apply what we learn in the lab to improve the lives of patients. The discoveries that we’re making today provide the foundation for the therapies of tomorrow.”

Here are some of the most exciting scientific discoveries reported over the past year, in chronological order.

CAR T Cells Show Promise Against Age-Related Diseases in Mice

Chimeric antigen receptor (CAR) T cells have transformed the treatment of blood cancers in recent years. And there have been positive signs that these “living drugs” can be harnessed against other diseases, such as autoimmune disorders.

Laboratory research led by MSK and Cold Spring Harbor Laboratory published January 24 in Nature Aging suggests these engineered immune cells also hold promise for treating some diseases related to aging — specifically, those caused by the accumulation of senescent cells (cells that stop dividing due to age or damage).

MSK and NCI Scientists Develop AI Tool to Predict How Cancer Patients Will Respond to Immunotherapy

Researchers at MSK and collaborators at the National Cancer Institute (NCI) developed an artificial intelligence (AI) tool that uses routine clinical data — such as information collected from a simple blood test — to predict whether someone’s cancer will respond to immune checkpoint inhibitors, a type of immunotherapy drug that helps immune cells kill cancer cells. The machine-learning model may help doctors determine if immunotherapy drugs are effective for treating a patient’s cancer. Their findings were published June 3 in Nature Cancer.

Fasting Primes the Immune System’s Natural Killer Cells to Better Fight Cancer, New Study in Mice Finds

Fasting and other dietary regimens are increasingly being explored as ways to starve cancer cells of the nutrients they need to grow and to make cancer treatments more effective.

Researchers from MSK’s Sloan Kettering Institute and their collaborators showed for the first time that fasting can reprogram the metabolism of “natural killer” immune cells, helping them to survive in the harsh environment in and around tumors, while also improving their cancer-fighting ability. The findings, published June 14 in Immunity, could help explain one of the mechanisms by which fasting may help the body defend against cancer — along with more generally reducing fat and improving metabolism. And while more research is needed, the results also suggest fasting could be a strategy to improve immune responses to make immunotherapy more effective, the study authors note.

Better Together: Spatial Arrangement of Three Immune Cells Is Key to Attacking Tumors

Researchers at MSK and Baylor College of Medicine in Houston, found that in order for immune cells to effectively kill the cells of a tumor, they need to take on a specific spatial configuration: a triad of three different immune cells.

Up until now, no one knew that these cells needed to be physically present together in tumors to generate an effective immune response against cancer cells. The discovery, which was published July 8 in Cancer Cell, has immediate therapeutic implications and could alter the way doctors administer immunotherapies.

TGF-Beta and RAS Signaling Are Both Required for Lung Cancer Metastasis, Study Finds

The TGF-beta and RAS signaling pathways work together to spur the spread of cancer in lung adenocarcinoma, a leading cause of cancer deaths around the world, a study by researchers at MSK’s Sloan Kettering Institute found.

Take away one of those two signals, and lung cancer will not be able to spread (metastasize) to new parts of the body, their findings in animal models suggest. The research, which appeared September 6 in Cell, points to new opportunities to potentially prevent metastasis, thanks to an updated understanding of the underlying processes.

New, Rare Type of Small Cell Lung Cancer Identified by MSK Research Team

A team of doctors and researchers at MSK identified a new, rare type of small cell lung cancer that primarily affects younger people who have never smoked.

Their findings, which include a detailed analysis of the clinical and genetic features of the disease, also highlight vulnerabilities that could help doctors make better treatment decisions for people diagnosed with it.

It’s not every day that researchers identify a new subtype of cancer. The findings, published August 26 in Cancer Discovery, present the team’s analysis and highlight the new disease type’s clinical and pathological features and distinct molecular mechanism.

New Insights Into Neuroendocrine Prostate Cancer, an Aggressive and Treatment-Resistant Type

Most prostate cancers are classified as adenocarcinomas, which rely on the androgen receptor (AR) to survive and grow. Over the past decade, several effective AR-targeting drugs have become available. But about 15% of these cancers completely change their identity to escape the effects of AR-targeting drugs — transforming from adenocarcinoma into neuroendocrine prostate cancer, a much more aggressive and deadly form of the disease.

Now an MSK team has developed a powerful new research tool for understanding how this transition unfolds. The new platform makes it possible to observe the switch in cell states from the earliest stage, enabling researchers to tease apart the genetic mutations and cell-to-cell signals critical to the lineage change. The findings, published October 11 in Nature Cancer, also are helping to shed light on the role played by the surrounding cells, known as the tumor microenvironment.

Unlocking the Secrets of Cancer Metastasis: MSK Study Provides New Insights, Potential Therapeutic Opportunities

Metastasis remains the primary challenge to reducing cancer deaths worldwide. Effective treatments against metastasis will require a deeper understanding of both the changes that happen when cells from a primary tumor metastasize and the mechanisms that drive those changes.

Now a unique study is providing insights into metastatic cells’ ability to access early developmental states, what scientists call “cellular plasticity.” Through this process, the cells in a metastasized tumor are radically different from those in the tumor where the cancer started. The differences between the two are critical, which researchers say points to new therapeutic opportunities. The findings were published October 30 in Nature.

MSK Research Reveals How Mitochondria Function Under Stress, Like in Cancer

Many learned in high school biology that mitochondria are the powerhouse of the cell. But that’s only part of the story.

A research team from MSK’s Sloan Kettering Institute has revealed new details about how mitochondria respond in times of stress, when nutrients are scarce and demand for both energy and cellular building blocks is high. In findings published November 6 in Nature, the researchers answer how mitochondria balance these two essential functions. The new findings not only answer a fundamental question about cell biology, they have direct implications for understanding cancer — the epitome of a stressful biological event.

Cancer Risk Declines in Old Age, New MSK Research Helps Explain Why

Age is considered the most important risk factor for cancer. That’s because genetic mutations build up in cells over years and decades, and ultimately drive the development of cancer.

A study from researchers at MSK and their collaborators provides new evidence about how advanced age can also be protective against cancer. The study, which was published in Nature on December 4, further points to the underappreciated role that iron plays in aging cells’ ability to regenerate — suggesting that therapies that target iron metabolism may work better in younger people than older ones.